Abstract
One of the most important enzymes in the catecholamine cycle, catecholamine-O-methyltransferase (COMT), plays a critical role in the extracellular metabolism of dopamine and norepinephrine both in the periphery and the central nervous system. COMT has attracted strong interest in regards to its role in dopamine-related pathologies, particularly Parkinson’s disease. There are several mechanisms for the potential involvement of COMT-related processes in the pathophysiology of Parkinson’s disease or the consequences of L-DOPA treatment. COMT-mediated metabolism of LDOPA in the periphery influences brain dopamine levels, while the product of central COMT-mediated dopamine metabolism, 3-methoxytyramine, can affect movement via interaction with Trace Amine-Associated Receptor 1 (TAAR1). COMT inhibitors have a long history of clinical use in the treatment of Parkinson’s disease. Several clinical genetic studies have shown that variants of COMT gene contribute to the manifestations or treatment responses of this disorder. Here, we review the basic molecular mechanisms that could be involved in COMT-dependent processes in Parkinson’s disease, the pharmacological properties of COMT inhibitors used in the treatment of this disorder and the clinical genetic observations involving COMT gene variants as modulators of pathological processes and responses to dopamine replacement therapies used in the treatment of the disorder.
Keywords: Dyskinesia, 3-methoxytyramine, trace amines, TAAR1, tolcapone, entacapone, nebicapone, Catechol O Methyl Transferase, Dyskinesia, L-DOPA, COMT, COMT Inhibitors, Parkinson's disease
CNS & Neurological Disorders - Drug Targets
Title:Role of Catechol-O-Methyltransferase (COMT)-Dependent Processes in Parkinson’s Disease and L-DOPA Treatment
Volume: 11 Issue: 3
Author(s): Stefano Espinoza, Francesca Manago, Damiana Leo, Tatyana D. Sotnikova and Raul R. Gainetdinov
Affiliation:
Keywords: Dyskinesia, 3-methoxytyramine, trace amines, TAAR1, tolcapone, entacapone, nebicapone, Catechol O Methyl Transferase, Dyskinesia, L-DOPA, COMT, COMT Inhibitors, Parkinson's disease
Abstract: One of the most important enzymes in the catecholamine cycle, catecholamine-O-methyltransferase (COMT), plays a critical role in the extracellular metabolism of dopamine and norepinephrine both in the periphery and the central nervous system. COMT has attracted strong interest in regards to its role in dopamine-related pathologies, particularly Parkinson’s disease. There are several mechanisms for the potential involvement of COMT-related processes in the pathophysiology of Parkinson’s disease or the consequences of L-DOPA treatment. COMT-mediated metabolism of LDOPA in the periphery influences brain dopamine levels, while the product of central COMT-mediated dopamine metabolism, 3-methoxytyramine, can affect movement via interaction with Trace Amine-Associated Receptor 1 (TAAR1). COMT inhibitors have a long history of clinical use in the treatment of Parkinson’s disease. Several clinical genetic studies have shown that variants of COMT gene contribute to the manifestations or treatment responses of this disorder. Here, we review the basic molecular mechanisms that could be involved in COMT-dependent processes in Parkinson’s disease, the pharmacological properties of COMT inhibitors used in the treatment of this disorder and the clinical genetic observations involving COMT gene variants as modulators of pathological processes and responses to dopamine replacement therapies used in the treatment of the disorder.
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Cite this article as:
Espinoza Stefano, Manago Francesca, Leo Damiana, D. Sotnikova Tatyana and R. Gainetdinov Raul, Role of Catechol-O-Methyltransferase (COMT)-Dependent Processes in Parkinson’s Disease and L-DOPA Treatment, CNS & Neurological Disorders - Drug Targets 2012; 11 (3) . https://dx.doi.org/10.2174/187152712800672436
DOI https://dx.doi.org/10.2174/187152712800672436 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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